Reproductive Medicine Pharmacology

• Mechanism:
• -GnRH analog
• -agonist properties when used in a pulsatile fashion
• -antagonist properties when used in continuous fashion (↓FSH, LH)

• Clinical Use:
• -infertility (pulsatile)
• -prostate cancer (continuous - use with flutamide)
• -uterine fibroids (continuous)
• -precocious puberty (continuous)

• Toxicity:
• -antiandrogen
• -nausea
• -vomiting

"Leuprolide can be used in lieu of GnRH"

• Mechanism:
• -agonist at androgen receptors

• Clinical Use:
• -hypogonadism
• -promotes development of secondary sex characteristics
• -stimulate anabolism to promote recovery after burn or injury

• Toxicity:
• -causes masculinization in females
• -reduces intratesticular testosterone in males by inhibiting release of LH → gonadal atrophy
• -premature closure of epiphyseal plates
• -↑ LDL
• -↓ HDL

• Finasteride
• Flutamide
• Ketoconazole
• Spironolactone

• Mechanism:
• -a 5α-reductase inhibitor (decreased conversion of testosterone to DHT)

• Clinical Use:
• -BPH
• -Male Pattern Baldness

To prevent male-pattern hair loss, give a drug that will encourage female breast growth

• Mechanism:
• -nonsteroidal competitive inhibitor of androgens at the testosterone receptor

• Clinical Use:
• -prostate carcinoma

• Mechanism:
• -inhibits steroids synthesis (inhibits 17,20 desmolase)

• Clinical Use:
• -PCOS (prevent hirsutism)

• Toxicity:
• -gynecomastia
• -amenorrhea

• Mechanism:
• -inhibits steroids binding (MC R antagonist that also affects androgen receptor)

• Clinical Use:
• -PCOS (prevent hirsutism)

• Toxicity:
• -gynecomastia
• -amenorrhea

• Mechanism:
• -bind estrogen receptors

• Clinical Use:
• -hypogonadism
• -ovarian failure
• -menstrual abnormalities
• -HRT in postmenopausal women
• -in men with androgen-dependent prostate cancer

• Toxicity:
• -increased risk of endometrial cancer
• -bleeding in postmenopausal women
• -vaginal clear cell adenocarcinoma in women exposed to DES in utero
• -increased risk of thrombi

• Contraindications:
• -ER positive breast cancer
• -history DVTs

• Clomiphene
• Tamoxifen
• Raloxifene

• Mechanism:
• -partial agonist at estrogen receptors in hypothalamus
• -prevents normal feedback inhibition and increased release of LH and FSH from pituitary, which stimulates ovulation

• Clinical Use:
• -infertility
• -PCOS

• Toxicity:
• -hot flashes
• -ovarian enlargement
• -multiple simultaneous pregnancies
• -visual disturbances

• Mechanism:
• -estrogen receptor antagonist on breast tissue

• Clinical Uses:
• -treat and prevent recurrence of ER-positive breast cancer

• Mechanism:
• -estrogen agonist on bone
• -reduces reabsorption of bone

• Clinical Uses:
• -osteoporosis

• Clinical Uses:
• -relief or prevention of menopausal symptoms (hot flashes, vaginal atrophy)
• -osteoporosis (increased estrogen decreases osteoclast activity)

• Toxicity:
• -unopposed ERT increases the risk of endometrial cancer (add progesterone)
• -possible increased cardiovascular risk

• Mechanism:
• -aromatase inhibitors

• Clinical Uses:
• -used in postmenopausal women with breast cancer

• Mechanism:
• -bind progesterone receptors
• -reduce growth and increase vascularization of endometrium

• Clinical Use:
• -used in OCPs
• -used in the treatment of endometrial cancer and abnormal uterine bleeding

• Mechanism:
• -competitive inhibitor of progestins and progesterone receptor

• Clinical Use:
• -termination of pregnancy
• -administered with misoprostol (PGE1)

• Toxicity:
• -heavy bleeding
• -GI effects (N/V, anorexia)
• -abdominal pain

• Mechanism:
• -estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge
• -no estrogen surge → no LH surge → no ovulation
• -progestins cause thickening of cervical mucus (limits access of sperm to uterus)
• -progestins also inhibits endometrial proliferation (makes it less suitable for implantation)

• Clinical Use:
• -contraception

• Contraindications:
• -smokers > 35 years (increased risk of CV events)
• -hx of thromboembolism and stroke
• -hx of estrogen dependent tumor

• Mechanism:
• -β2 agonist
• -relaxes uterus

• Clinical Use:
• -reduce premature uterine contractions

• Mechanism:
• -α1-antagonist
• -inhibits smooth muscle contraction
• -selective for α1AD receptors on prostate (not vascular receptors)

• Clinical Use:
• -BPH

• Mechanism:
• -inhibit PDE5
• -causes increased cGMP → smooth muscle relaxation in corpus cavernosum
• -increases blood flow and penil erection

• Clinical Use:
• -erectile dysfunction

• Toxicity:
• -HA
• -flushing
• -dyspepsia
• -impaired blue-green color vision
• -risk of life-threatening hypotension in patients taking nitrates

"Sildenafil and vardenafil fill the penis"

"Hot and sweaty" but then Headache, Heartburn and Hypotension"

• Mechanism:
• -synthetic androgen that acts as partial agonist at androgen receptors

• Clinical Use:
• -endometriosis
• -hereditary angioedema

• Toxicity:
• -weight gain
• -edema
• -acne
• -hirsutism
• -masculinization
• -decreased HDL levels
• -hepatotoxicity